Autoantibodies to a 52kd Ro/SSA protein occur in some patients with SLE, and are inversely correlated with renal disease in Black American SLE patients. A polymorphism of the 52kd Ro gene correlates with this finding, leading to the hypotheses in this project that, first, this polymorphism may be a genetic marker for an allelic variant of 52kd Ro which preferentially occurs in lupus patients, or secondly, that this polymorphism is a marker for a mutation which disregulates the expression of this gene. Sequence analysis and functional promoter studies will be used in Aim 1 to address these hypotheses. In Aim 2, the DNA binding properties of the 52kd Ro protein will be investigated and the possible role of this protein influencing gene expression will be studied. Aim 3 will quantitate antibodies to 52kd Ro in subsets of lupus patients and Aim 4 will study the pathogenicity of these autoantibodies focusing on lesions of cutaneous lupus and binding of these autoantibodies to kerotinocytes after UV irradiation, a trigger for the photosensitive reactions of cutaneous lupus patients.